Careers in Nature – 1 August 2014

NatureEvery fortnight we’ll be collating all the careers related content across Nature, just in time for some weekend reading.

Career paths have twists and turns. They’re never straight forward, however much time you spend planning them. One single email changed the careers of Anthony Barnosky and his wife, Elizabeth Hadly. They had co-authored a paper in Nature about climate change (Barnosky, A. D. et al. Nature 486, 52–58 (2012)), and the media attention it created caught the eye of Jerry Brown, the governor in California. He wanted them to turn their paper into a consensus statement – a document that could be used in political circles, and could be understood by political leaders, policy makers and the public. Read more from Virginia Gewin on this story of politics and science.

The Scripps Research Institute president, Michael Marletta, has resigned from his post after the faculty rebelled against him. The reason for the rebellion is that Marletta had started making plans to join the research institute with the Los Angeles based University of Southern California. Read more about the Scripps president’s resignation on the Nature News blog. Continue reading

NIH Common Fund song & video contests

“We want to know whether our future baby’s health is based on genes or the environment.” This is a concern shared by a lot of would-be parents for sure, and is the question posed to Dr. M. Elizabeth Ross at the beginning of this short video. The video, made by the labs of Dr. Ross and Dr. Christopher E. Mason at Weill Cornell Medical College is part of a competition sponsored by the NIH to commemorate the 10th anniversary of the Common Fund.

Logo for the NIH Common Fund 10-Year Commemoration Song & Video Competitions

The video takes a tongue-in-cheek approach to explaining an NIH-funded project investigating the role of epigenetic changes in birth defects. The contest ends tomorrow, May 9, and the results will be determined by the number of “Likes” the videos receive on YouTube.

To vote for this or any of the other amazing videos (and songs), check out the contest page here.

 

Brain initiatives galore, smiles aplenty

Vivien Marx reports on the Society for Neuroscience meeting in San Diego and the big brain projects in the EU and US.

SfN attendance sign

The Society for Neuroscience annual meeting in San Diego clocked record attendance.{credit}Vivien Marx{/credit}

The brain is hot.

Despite dismay about the recent 16-day US government shutdown, the impact of automatic budget cuts–the sequester–taking effect in light of federal budget disagreements in Washington, and the general economic malaise, there is palpable excitement. New large-scale initiatives are getting underway around the world to develop technologies to empower neuroscientists.

This year’s Society for Neuroscience (SfN) meeting in San Diego that has just ended, clocked a record attendance of over 30,000 attendees, noted society president Larry Swanson to attendees with a broad smile in one of his conference announcements. “It is an inspirational time to be a neuroscientist,” he said, with the field drawing attention, for example, across the European Union and in the White House. In a town hall meeting for the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, there was no lack of critical comments and suggestions of aspects to include in BRAIN. But smiles stayed plentiful as funders explained their plans.

The fact that the US president chose neuroscience as his multi-year, signature project is something “we should all be pretty excited about,” says Tom Insel, director of the National Institutes of Mental Health. In addition to projects in the US, such as  (BRAIN) Initiative and the EU’s Human Brain Project, large neuroscience projects are just emerging in Australia, China, Japan and Israel. “This is beginning to feel like a global movement,” he says. And projects are unfurling in the private sector, too.

The new tools, says Story Landis, director of the National Institute of Neurological Disorders and Stroke, will help neuroscientists do their work “bigger, better, faster” and expand the research strides made in recent years.

Much remains to be done. Compared to what is known about the kidney or heart, very little is known about the brain, says Insel. Adding to the neurological diseases, he noted, are the “invisible wounds of war” such as traumatic brain injury and post-traumatic stress disorder. Tools to help diagnose these illnesses are urgently needed.

Nora Volkow, director of the National Institute of Drug Abuse says that the BRAIN initiative stands to “act like a catalyst” in ways not unlike the decoding of the human genome and its successive “avalanche of discovery.”

Besides attending SfN’s hundreds of sessions and 17,000 posters, scientists had the chance to get up close and personal with representatives from the funding agencies and to hear about and discuss the new opportunities. Here is a snapshot of some of the announcements.

European Union
As Daniel Pasini from the European Commission’s programme on future and emerging technologies explained, the 10-year European Human Brain Project has invited the scientific community to present “grand ideas” for a massive effort to computationally reconstruct the human brain using supercomputers.

The model will help to study brain-related diseases, which are a major health challenge, an economic and social burden, and to pool data and expertise more effectively and translate results for treatments.

The project, which took three years of planning, involves over 250 scientists across Europe in 135 research groups in 22 countries, including groups in the US and Asia. The program began officially in October and has a budget of $1.6 billion. Half of the money will come from the EU the other will come from national funding sources, Pasini says. The first phase is slated to last 30 months and is funded with $100 million.

Six platforms are to be developed including, for example, the neuroinformatic platform as a single point of access to all neuroscience and clinical data along with software tools. The other platforms involve brain simulation, high performance computing, medical informatics, neuromorphic projects and neurorobotics. The idea is to keep improving the model as new data become available. All tools and data are set to be made available to the global scientific community. The plan is to create the ‘CERN for brain research.’ Not unlike a telescope facility or a super-collider, scientists will be able to perform experiments and use this platform to help continue to expand the model.

Deconstructing Henry

The Brain Observatory at UC San Diego is running ‘Deconstructing Henry’ an examination of the Brain of patient H.M.{credit}Vivien Marx{/credit}

US Defense Advanced Research Projects Agency (DARPA)
“Yes, we build guns and bombs, that is true,” says Colonel Geoffrey Ling of DARPA more generally. He is a neurologist who also served in Afghanistan and Iraq and currently deputy director of DARPA’s division responsible for defense sciences, which does not build bombs and guns. He and many other neuroscientists want to cure diseases ranging from Alzheimer’s to schizophrenia to post traumatic stress disorder to traumatic brain injury. DARPA is indeed “zeroed in” on the problems facing soldiers returning from the battlefield.

Speaking directly to fellow panelists from NIH, he says: “I wish they would double the budget yet again for you guys,” which was greeted by SfN attendees with vigorous applause.

Two DARPA solicitations for proposals are now open, offering “real money,” as Ling says, collecting projects that relate to memory dysfunction and psychiatric disorders. More solicitations are “in the works,” he says. “It’s not for us to decide what you’re going to build,” he says, highlighting the importance of imagination and taking a diversity of approaches.

The funding model at DARPA is shaped by use cases to assure that what is developed serves his constituency, the servicemen and women.

Multidisciplinary research, for example, is not achieved with the collaboration of a cellular neuroscientist, a neurophysiologist, and a neurologist. Rather, for DARPA interdisciplinary efforts can be a team comprised of a mathematician, a physicist and “a crazy guy in his backyard putting together some Rube Goldberg thing,” says Ling.

Unlike NIH, DARPA issues no grants but rather contracts, which are “deliverables-driven,” and may seem more rigid that NIH. But he sees strength in the synergy of the different funding approaches by NSF, NIH and DARPA. DARPA is committed to this project over the next decade, says Ling.

Data-sharing provisions are built into each contract, which DARPA takes “extremely seriously,” and breach of contracts are pursued. The DARPA solicitations issued are just the beginning, he says.

Systems based Neurotechnology for Emerging Therapies (SUBNETS)
Deadline: Dec. 17, 2013
This project seeks proposals to develop devices, perform model organism based research, or enable modeling of human neural systems, which are geared to help treat patients with neuropsychiatric and neurologic disease.

Restoring Active Memory (RAM)
Deadline: Jan. 6, 2014
This project seeks proposals in the area of analyzing and decoding neuronal signals which can be used to help patients recover memory function after injury.

SfN attendee bag

Companies in the neuroscience field may benefit from funding in the emerging large-scale projects. Here a scientst at SfN wears one company’s advertisement.{credit}Vivien Marx{/credit}

National Institutes of Health (NIH)
No grants have yet been awarded through the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. But grants are in the pipeline. True, says Insel, some see the project as a perhaps $40 billion dollar challenge, but he views the funding in 2014 as an “initial investment.”

The first report of the BRAIN initiative’s working group, says Landis, offers a guide for how the project could begin to move forward in its first year. The working group, is the advisory committee to the NIH director is chaired by Rockefeller University’s Cornelia Bargmann and Stanford University’s Bill Newsome. Landis says excitement is high in the Obama administration and across NIH. The hope is that this enthusiasm would be reflected in the budget allocations.

The NIH first year funding is “a down payment,” she says.

Insel says that the NIH’s $40 million to be allocated in 2014 is drawn from the following sources:

  • $10 million are coming from the NIH Director’s discretionary fund
  • $10 million are from the NIH Blueprint Neuroscience a program to enhance collaboration across NIH institutes
  • $20 million are split among four NIH agencies: National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Mental Health (NIMH), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institute of Drug Abuse (NIDA)

These monies were previously slated for initiatives of the individual institutes’ choice. As Landis explains, these four agencies agreed that the BRAIN Initiative was the one they selected for fund allocation. She says she and her colleagues are “optimistic” that the excitement, opportunities and promise of the BRAIN initiative will power the budgets of the future. Throughout sessions at SfN, she, Insel and others were quick to squelch fears that BRAIN would draw funding away from investigator-driven grants.

The first NIH Requests for Applications (RFAs) are currently begin hashed out with cross-communication happening across NIH, NSF and DARPA, says Insel.

All BRAIN Initiative projects will be peer-reviewed and perhaps unlike the more classic grants, they will have milestones and there will be expectations of data-sharing. “That’s going to be baked into everything we do in this project,” says Insel. Evaluations will accompany the projects after they are funded.

A number of awards are likely to be cooperative agreements, which are part way between a contract with deliverables and R01s, says Landis. These agreements are accompanied by milestones. If researchers do not share data and that provision is in their notice of grant award “there can be consequences,” she says.

Update: In mid-December NIH announced six funding opportunities. Approximately $44 million will finance six new funding opportunities.

Sunset at SfN

Two of the 30,000 attending scientists take a break outside the SfN conference halls.{credit}Vivien Marx{/credit}

National Science Foundation (NSF)
Cora Marrett, the acting director of the NSF says her agency will “very energetically” support the BRAIN Initiative. She says that funders need to take “the long view” to let the forces of scientific discovery play out with a long-term commitment. “I’m feeling very optimistic, too, about what the long-run prospects for additional resources will look like.”

Evidence of NSF’s engagement with neuroscience in general can be seen in the recent $25 million grant to fund the Center for Brains, Mind and Machines at the Massachusetts Institute of Technology. The intent is to blend computer science, math, robotics, neuroscience and cognitive science.

The BRAIN Initiative will require intense collaboration across disciplines and scales, she says. Neuroscience has been more devoted to small science, she says, the work of individual principal investigators and small lab groups. Marrett agrees with Alan Leshner, the executive publisher of Science, that neuroscience’s strides will benefit from a change in the culture toward larger-scale, interdisciplinary efforts.

At the same time, this shift will occur without prescriptions that all work needs to be on “the huge scale” of a particle accelerator, for example. Indeed neuroscientists will need to integrate findings across the scales of their research and link physiology, biophysical and genetic data with cognitive and behavioral findings (see Leshner Editorial in Science).

The projects will require data management plans of the grantees, she says, to explain how they will handle data-sharing, which is to the benefit of the entire enterprise.

Seeing through the smoke with the help of research: a conversation with Helen Meissner

{credit}NIH{/credit}

Most people stopped doubting the dangers of tobacco long ago. And yet, tobacco products continue to adorn the checkout kiosks of convenience stores and appear in the pages of magazines. The question is: which of these products should be allowed and which should not? It’s no longer a theoretical question: the US Food and Drug Administration (FDA) was granted the power to regulate these products four years ago.

More research will help the FDA make tough decisions in this area, says Helen Meissner, the director of the Tobacco Regulatory Science Program at the US National Institutes of Health (NIH). Meissner is leading a joint effort with the FDA to study how to bring science-based regulation to the manufacturing, marketing and distribution of products such as cigarettes. On 19 September, the two agencies announced that they would grant a total of $53 million to 14 research teams working on tobacco-related projects across the US. Nature Medicine asked Meissner about the newly formed Tobacco Centers of Regulatory Science (TCORS) and the challenges of government-funded research in this space.

What are the biggest research goals of this new funding effort, broadly speaking?

The FDA [needs] to understand tobacco products in order to review tobacco products. They need product standards. They need to know how best to monitor compliance and enforcement, say with advertising or youth access. And they also need information on the best ways to communicate about tobacco products through media and education campaigns.

And how will the 14 centers come together and communicate?

They will be coming together through grantee meetings, so there will be collaborative activities across the centers. Although each is independent and they have different seams—as I mentioned they cover different areas—there is synergy as well across the centers. So that is the role of NIH: to convene the groups.

Continue reading

The NIH’s BRAIN Initiative interim report – notes and thoughts

The first official report lists the scientific priorities that will be funded by the NIH as part of the BRAIN Initiative

brain_map

{credit}Margrie & Osten, Nat. Methods{/credit}

Yesterday evening we heard the first official report that delivered some details about what scientific areas the BRAIN Initiative (at least the part coordinated by the National Institutes of Health) will focus on and what its general approach to science funding will be.

Cori Bargmann and Bill Newsome (co-chairs of the NIH-appointed panel that is advising the NIH-director about the plan) spoke through a webcasted seminar to explain the conclusions that arose from the series of scientific workshops and meetings that have been taking place over the summer to discuss what could be the scientific priorities of the BRAIN Initiative. These priorities will set the ground of the research areas to be funded by the BRAIN initiative NIH funding in Fiscal Year 2014 (with a budget of US $40M).

The overall goal of the project was summarized as focusing of developing tools and resources for analyzing neuronal circuits and their function in living organisms.

The two scientists delved on a number of principles that applied to the overall initiative, such as promoting platforms for data sharing, promoting interdisciplinary research and focusing on a variety of experimental organisms and studies across temporal and spatial scales.

The specific areas that will be funded through the Initiative are summarized below:

  1. Generate a census of cell types in the nervous system. Including neurons and glia and techniques for targeting them. To be attempted in parallel in human and animal samples. Methods developed for this should apply across species.
  2. Create structural maps of the brain. This means cell to cell level connections in different animal models. This would complement the Human Connectome project (based on macroscale neuroimaging approaches).
  3. Develop new large scale methods for recording chemical and electrical activity of neurons. Scaling up of electrophysiological and imaging methods as well as completely new technologies.
  4. Develop a suite of tools for circuit manipulation and perturbation of circuit function. A push for the development of technologies like optogenetics that enable manipulating nervous activity in ways that resemble natural activity patterns.
  5. Linking brain activity to behavior. Activity monitoring at the same time that behavior is monitored. Highlighting the importance of making simultaneous measurements during long periods of time and during different types of behaviors.
  6. Integrating theory, statistics and computation with experimentation. Importance of theoretical frameworks that could explain principles of brain function.
  7. Delineate mechanisms underlying macroscale brain imaging technologies, as used in humans.
  8. Create mechanisms to enable collection of human data.
  9. Provide training so that new methods reach the community and promoting interdisciplinary research.

Although these FY2014 research priorities are presented as 9 independent entities, the goal is really to integrate these approaches as much as possible —but how exactly this integration will take place or be promoted is to be revealed by June 2014.  The goals are also highly ambitious and will require much more funding than the BRAIN Intiative’s current budget.

The speakers noted that the goals were not “to develop tools for tools sake” but tools that could have applicability. Innovative tools, thoroughly validated and applied in real nervous systems, improved through iterations and to ensure that they are disseminated efficiently to the community.

The commission also highlighted that their goal was not to deliver the solutions but the problems. Solutions to addressing these challenges are to come from ‘bottom-up’ approaches proposed by the community of scientists.

Tools for studying individual cells in the brain or the entire brain as a whole exist and continue to be very useful. But methods for understanding how connected networks of cells in the brain work and relate to behavior are still largely missing. Even maps of these connected entities remain unknown. Focusing funding on better tools to close this gap will be exciting and productive for advancing neuroscience as a whole.

The conclusions disclosed in this interim report are very much in line with what was expected of the project as announced a few months ago. They also largely agree with the main scientific goals that were deemed to be the top funding priorities for the National Science Foundation for the BRAIN Initiative (which will have US$20M to contribute, as well). Indeed, many of the topics covered in these 9 areas were things we and others discussed in editorials and commentaries related to the BRAIN Initiative in our pages and in this blog. The working group that has developed these priorities has had an inclusive, overarching frame of mind and included most of the major challenges that neuroscience currently faces, as most scientists would probably agree.

As we’ve said before, a push for technology development in neuroscience, with clear goals and challenges that these tools need to tackle, will surely be an efficient way of advancing the science of the brain.

US budget cuts imperil domestic and global biomedical research

{credit}Shutterstock{/credit}

In the medical world, the term ‘sequestration’ is usually preceded by the word ‘pulmonary’ or ‘splenic’ and is used to describe rare diseases that are the focus of research grants funded by the US National Institutes of Health (NIH). But sequestration has now taken on a new meaning.

On Friday (1 March), a series of sweeping federal budget cuts totaling more than a trillion dollars over the next ten years are scheduled to automatically go into effect unless a legislative bargain is reached—and their impact on biomedical research could be dire, with consequences felt both in the US and abroad.

“We are going to maim our innovation capabilities if you do these abrupt deep cuts at NIH,” former agency director Elias Zerhouni, now head of global R&D at the French drug company Sanofi, told the Washington Post. “It will impact science for generations to come.”

The NIH, already suffering through half-a-decade of stagnant funding, will receive a 5.1% cut across the board—a reduction of $1.5 billion from a total budget of $31 billion. Should this happen, the agency’s operation plan is straightforward: fewer projects will get new funding and existing ones will be supported at lower levels. “Cuts will result in slower progress against our most common diseases, such as Alzheimer’s, cancer, AIDS, diabetes and heart disease,” Francis Collins, the NIH’s current director, said at a press conference addressing sequestration last week.

United for Medical Research, a coalition of universities, biotech companies and research associations, estimates that cuts to the NIH budget could lead to 20,000 fewer jobs and a $3 billion economic impact this fiscal year. Potentially more troubling is the effect of sequestration on new researchers. Lower success rates for NIH grants, which have steadily declined since their peak in the early 2000’s, could stall the careers of young investigators. Even training grants, which fund graduate students at universities, are at risk of being cut, said Collins. “This is not a spigot you turn off and turn back on later. If we lose the talents of this up and coming generation, they’re not coming back,” he said.

Although the NIH is the single largest funding source for biomedical research, other agencies—including the Food and Drug Administration, the Agency for Healthcare Research and Quality, the Department of Defense, the Centers for Disease Control and Prevention, the National Science Foundation, and the Agency for International Development—would all receive sequestration cuts.

Combined, the US agencies are the largest funder of research in the world. Their significant contributions to global health and the potential harm sequestration could cause are highlighted in a report released today by the Global Health Technologies Coalition, a group of nonprofit organizations.

With the development of potential HIV preventatives, improved malaria drugs and other global health products, US government research funding has already saved millions of lives and provided economic benefits around the world. If the research pipeline were to be interrupted now, scientific regression, increased long-term costs and needless deaths would result, the report argues. “There is much to lose by pulling back now,” the authors write.

In Massachusetts, nine NIH-funded research projects in this year’s $10 million club

 

So far for 2012, the NIH has approved 3,810 grants in Massachusetts – some for new projects, others for familiar, ongoing research centers. The big money is going to genetics, HIV/AIDS and biodefense. Few topped $10 million –according to NIH, the av

erage award amount nationwide was $44,642 for 2011. Among the group – genomics superstar Eric Lander, whose name cam

Here’s a look at the projects that, so far this year, have broken the $10 million mark – and a few that come close.e up during the recent presidential search at MIT and Daniel Kuritzkes at the Brigham, who got a standing ovation at the recent AIDS conference when he annouced findings on two more AIDS patinets who became virus-free after bone marrow transplants.  Also note that Harvard Med School dean Jeffrey Flier is listed as the PI on the grant to the troubled primate research center. Continue reading

Congressman criticizes US handling of H5N1 papers

Congressman Jim Sensenbrenner of Wisconsin{credit}https://sensenbrenner.house.gov/{/credit}

An influential member of the US Congress remains dissatisfied with the government’s handling of two research papers on mutant forms of avian influenza, and is threatening legislation to control the controversial research.

Jim Sensenbrenner (Republican, Wisconsin) today said that the lack of a cohesive policy for handling risky research funded by the National Institutes of Health (NIH) and other federal agencies could necessitate new laws, a situation that researchers have been trying to avoid. “I prefer not to pursue legislation on this issue, with the hopes the scientific community can create its own approach. But failing a consequential … policy, Congressional action could be required,” Sensenbrenner told Nature in a statement.

The second of the controversial papers showing that H5N1, or ‘bird flu’, can spread through the air between mammals was published last week, providing some closure to the months-long debate about the work and whether its publication would result in the proliferation of dangerous viruses and increased risk of an accidental or intentional release. Sensenbrenner says not enough work has been done to ensure that such controversies don’t arise again.

On 21 June, NIH director Francis Collins responded to some pointed questions issued by Sensenbrenner’s office after a 29–30 March meeting when the National Science Advisory Board for Biosecurity (NSABB) reversed its initial opposition to the publication of the papers, in light of some manuscript revisions and the addition of data. Sensenbrenner, who is the vice-chairman of the Congressional committee on science and technology and sits on a subcommittee on terrorism and homeland security, had requested details on the provenance of a new government policy on reporting and overseeing ‘dual-use research of concern’ (DURC), research that could conceivably be put to nefarious ends.

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Who’s getting grants in Boston as NIH cuts back? New research funding for May

Nearly $8 million in NIH funding for new projects flowed into Massaschusett in May. Here’s a sample, with links to labs and full project descriptions:

  • $936,346 for strategies to treat antibiotic resistant bacteria to Harvards Thomas Bernhard

IDENTIFYING AND VALIDATING NEW ANTIBIOTIC TARGETS IN CELL WALL SYNTHESIS PATHWAYS New strategies to treat antibiotic resistant bacterial infections are sorely needed. This project combines small molecules and genetic methods to identify and validate new antibiotic targets in the pathway for assembly of the bacterial cell wall. The proposed work may lead to new therapies against methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative ESKAPE pathogens.

 Dr, Bernhard will be giving a talk on his work on June 21 at The Forsyth Institute, Seminar Room A, 245 First Street, 17th Floor, Cambridge, at Noon, on “The ABCs of Bacterial Cell Division,” as in ABC tranporters.

  •   $356, 356 for a prospective study looking at fat consuption and and breast cancer to Heather Eliassen  at the Brigham and Women’s hospital

CIRCULATING FATTY ACIDS AND BREAST CANCER RISK: A PROSPECTIVE STUDY  Fat intake has long been hypothesized to increase breast cancer risk, but cohort studies have not shown strong associations with total fat. This proposal seeks to expand our knowledge of the role of fat in breast cancer etiology by measuring specific fatty acids in the blood, representing fats from meat and dairy, processed foods, and vegetable sources, areas where dietary evidence suggests an association, as well as a marker of the internal transformation of fats with breast cancer risk. Characterizing these associations and further exploring potential mechanisms, will provide important knowledge about breast cancer prevention.

  •  $677, 984 for a exome chip data on 1,800 ADHD probands and their parents to Benjamin Neale at the Broad Institute

QUANTIFYING THE IMPACT OF RARE MUTATIONS ON ADHD We will generate exome chip data on 1,800 ADHD probands and their parents. The exome chip provides the first look at rare variation in the coding regions of genes that is heavily enriched for potential biological function. We will comprehensively analyze this data at a single locus, gene, and biological pathway level. This experiment promises to quantify the impact of rare mutations on ADHD.

  • $304,950 for research using in vitro studies to reveal biochemical and physiological functions of ribosome specialization to Wendy Gilbert at MIT.

FUNCTIONAL CONSEQUENCES OF RIBOSOME HETEROGENEITY:Translational regulation is essential for human health and development, but only a handful of translational regulatory mechanisms are understood. The proposed work will provide the first detailed understanding of the biochemical and physiological functions of ribosome specialization, an under-studied topic in the translational control field. We anticipate that our results will have broad implications for the study of eukaryotic gene expression, and will also illuminate the etiology of disease states, including cancer, that are associated with dysregulation of ribosome function.

  •  $278,213 for research into virulence factors secreted by many different pathogenic bacteria Alejandro P. Heuck at UMass medical school in Worcester

MOLECULAR MECHANISM OF TRANSLOCON ASSEMBLY INTO CELL PLASMA MEMBRANES I have developed a set of fluorescence techniques that have been successfully used to characterize the structure and pore-formation mechanism of various homo- oligomeric cytolytic toxins. I now propose to extent the use of these techniques to multi- protein transmembrane complexes, like the T3S translocon. The fluorescence approach will be combined with other biochemical and biophysical techniques (e.g., electrophysi- ology measurements, single molecule techniques, and cryo-electron microscopy) to un- ambiguously address fundamental structural aspects of the T3S translocon structure and assembly. By selective incorporation of various probes (e.g., environment-sensitive fluorophores, crosslinkers, gold-nanoparticles, charged groups, etc.) in the P. aerugi- nosa translocators, we will experimentally identify, among other things: which segments of these proteins are essential to determine the characteristics of the translocon channel, what segments form the contact interface between the needle and the translocon, and how the translocators are arranged in the translocon complex formed in the mammalian cell membrane..

NCATS inks drug-screening partnership with Lilly

The drug company Eli Lilly will screen more than 3,800 approved and investigational medicines to find potential new uses for the drugs in a partnership with the US National Center for Advancing Translational Sciences (NCATS).

The medicines are part of the NCATS pharmaceutical collection. Results of the screening, which will take place over the next 12–18 months, will be posted publicly at the pharmaceutical collection’s website, Lilly and the National Institutes of Health said today in a press release.

NCATS, the newest center at the National Institutes of Health (NIH), opened its doors this January. Its goal is to speed the time and decrease the cost it takes to bring new drugs to market. Critics have suggested that it will be difficult for the NIH to do what the drug industry has already tried and failed to do.

But NCATS acting director Thomas Insel said that the new partnership is an example of how NIH can play a unique part in drug development.

“Working together, we can make drug development pipelines more productive. The key is precompetitive collaboration to benefit all partners, ensuring broad access to the results,” Insel said in the NIH press release.